This proposal describes a carefully supervised program that will provide the applicant with the research skills and training required to study the potential contributions of genetic predisposition and allergen exposure to the phenotypic expression of childhood asthma. It will test the general hypothesis that cockroach allergen induces and worsens childhood asthma. This work is particularly relevant given the recent advances in asthma research which identify cockroach allergen as an extremely important indoor allergen. It may be responsible for increased prevalence, morbidity and mortality of childhood asthma in certain populations. The aims of this study are to extend earlier inquiries into cockroach allergen exposure and childhood asthma, a novel model which the applicant developed under the guidance of Peyton Eggleston, M.D. Professor of Pediatrics at The Johns Hopkins University School of Medicine. The immediate goals are to determine if: i) Young children with a strong family history of atopic asthma exposed during infancy to cockroach allergen have increased risk of sensitization to cockroach allergen compared to children with similar sociodemographic and family histories who are not exposed or who have low levels of exposure to this antigen ii) Children exposed to cockroach allergen in infancy have increased risk of developing childhood asthma compared to children who are either not exposed or exposed to low levels of the antigen iii). Cockroach allergen exposure increases the risk of young children having severe asthma thus determining if the intensity and duration of exposure relate to the severity of asthma. Potential enrollees will be among neonates of asthmatic mothers participating in studies conducted within the Maternal-Fetal Medical Units (MFMU) at the University of Chicago. The University of Chicago MFMU is a member of NHLBI/NICHD sponsored multicenter network of MFMUs (through grant U1O HD 27861-05). Cord blood will be analyzed for DNA, total IgE, lgA, Interleukin 4 (IL4) and Interferon (IFN) gamma. This prospective study will examine the presence, degree and duration of cockroach allergen exposure in the homes of these children over a 48 month period and relate the allergen levels to sensitization to cockroach allergen, the primary outcome variable. Exposure will also be related to occurrence of asthma and its severity. Accounting for a small dropout rate and the potential confounding variables, a sample size of 100 was selected which will provide over 80% power to detect an association in the sensitization rate from 5% in those with little or no exposure to 35% in those with high levels of exposure. Alan Leff, M.D. and the stimulating, productive, and the critical environment within the University of Chicago will foster the applicant's progression to independent lines of investigation. Insights gained from this work may lead to preventive measures which may reduce the prevalence and morbidity of childhood asthma.